Association Between Soluble Intercellular Adhesion Molecule-1 and Intracerebral Hemorrhage Outcomes in the FAST Trial

Abstract

BACKGROUND: Neutrophil-mediated inflammation in the acute phase of intracerebral hemorrhage (ICH) worsens outcome in preclinical studies. sICAM-1 (soluble intercellular adhesion molecule-1), an inducible ligand for integrins and cell-cell adhesion molecules, is critical for neutrophil extravasation. We aimed to determine whether serum levels of sICAM-1 are associated with worse outcomes after ICH. METHODS: We conducted a post hoc secondary analysis of an observational cohort using data from the FAST trial (Factor-VII for Acute Hemorrhagic Stroke Treatment). The study exposure was the admission serum level of sICAM-1. The coprimary outcomes were mortality and poor outcome (modified Rankin Scale score 4–6) at 90 days. Secondary radiological outcomes were hematoma expansion at 24 hours and perihematomal edema expansion at 72 hours. We used multiple linear and logistic regression analyses to test for associations between sICAM-1 and outcomes, after adjustment for demographics, ICH severity characteristics, change in the systolic blood pressure in the first 24 hours, treatment randomization arm, and the time from symptom onset to study drug administration. RESULTS: Of 841 patients, we included 507 (60%) with complete data. Hematoma expansion occurred in 169 (33%), while 242 (48%) had a poor outcome. In multivariable analyses, sICAM-1 was associated with mortality (odds ratio, 1.53 per SD increase [95% CI, 1.15–2.03]) and poor outcome (odds ratio, 1.34 per SD increase [CI, 1.06–1.69]). In multivariable analyses of secondary outcomes, sICAM-1 was associated with hematoma expansion (odds ratio, 1.35 per SD increase [CI, 1.11–1.66]), but was not associated with log-transformed perihematomal edema expansion at 72 hours. In additional analyses stratified by treatment assignment, similar results were noted in the recombinant activated factor-VII arm, but not in the placebo arm. CONCLUSIONS: Admission serum levels of sICAM-1 were associated with mortality, poor outcome, and hematoma expansion. Given the possibility of a biological interaction between recombinant activated factor-VII and sICAM-1, these findings highlight the need to further explore the role of sICAM-1 as a potential marker of poor ICH outcomes.

Astrocyte‐Derived Extracellular Vesicular miR‐143‐3p Dampens Autophagic Degradation of Endothelial Adhesion Molecules and Promotes Neutrophil Transendothelial Migration after Acute Brain Injury

“…This could be due to the fact that neutrophils are the first cells to respond and migrate from the peripheral blood to the brain after a stroke in the acute period. [ 46 , 47 ] To assess whether the significant differences in neutrophils were due to higher levels of circulating neutrophils in ATP6V1A CKO mice, blood samples were collected and circulating neutrophils were compared (Figure S6A , Supporting Information). The neutrophil counts in the peripheral blood were comparable between ATP6V1A fl/fl ICH and ATP6V1A CKO ICH mice (Figure S6B , Supporting Information).…”

Emerging diagnostic markers and therapeutic targets in post-stroke hemorrhagic transformation and brain edema

“…Intercellular Adhesion Molecule-1 (ICAM-1) on the endothelial cells facilitates the binding and transmigration of leukocytes, especially neutrophils, and monocytes, into the brain tissue ( Huang et al, 2022 ; Witsch et al, 2023 ). ICAM-1 can bind integrins on leukocytes, facilitating their adhesion to the endothelium ( Singh et al, 2023 ).…”

A Microfluidic Experimental Method for Studying Cell-to-Cell Exosome Delivery–Taking Stem Cell–Tumor Cell Interaction as a Case

“…Nanoparticles are similar in size to EVs (Figure 2k,l), so the EVs released by the stem cells inside the cell nest will show an equal distribution and deposition to nanoparticles due to the physical characteristics of EVs that are not easy to spread [8]. Exosomes have been observed to diffuse far from the site of secretion [19] or remain close to the cell surface [20,21].…”

“…Therefore, studying the dynamics of exosome packaging and transport and accurately quantifying packaged molecules' long-range action mechanisms is essential. At the same time, those soluble molecules that are not packaged, such as soluble intercellular adhesion molecules [8], also participate in cell-to-cell communication. Studying the detailed process of exosomes in cell-cell communication faces significant technical challenges because the transfer process of exosomes between living cells cannot be directly controlled, and only exosomes can be extracted for experiments.…”

“…In addition to separation from EVs by centrifugal precipitation [5], exosomes can be subdivided according to size, content, function, and source heterogeneity [3]. Exosome secretion kinetics [8] have also been studied to a certain extent. The velocity distribution during exosomes' motion on the cell surface is also measured more accurately (about 100 nm s −1 ).…”